Aging is a natural phenomenon with which any individual is confronted. It is inevitably accompanied by a reduction in the cell activity of the human body.
The most visible signs of age appear on the face: the skin slackens and the first wrinkles appear. Many solutions have been developed for attempting to slow down the occurrence of these signs of age or to repair already established signs.
Among these solutions, mention may be made of a technique which consists of injecting into or under the skin so-called filling substances, these substances may be resorbable or non-resorbable in vivo. The role of these substances is to fill the collapsed portions by creating volume in or under the skin, for treating different portions of the body, in particular the face. By this mechanical effect, the skin is re-tensioned and the wrinkles are smoothed, leading to a younger appearance of the treated area.
Among the so-called resorbable filling substances, mention may be made of crosslinked hyaluronic acid (HA) (also called «stabilized HA») used in dermal aesthetics. It is injected into or under the dermis in order to fill wrinkles or restore the volume of various areas of the body for a period of several months. It has the advantage of having very little secondary effects in post-injection and extremely rare complications in the long term. On the other hand, in the case of a bad injection, the practitioner has the possibility of correcting his/her treatment by injecting a solution of hyaluronidases (specific enzymes of HA), a solution which will degrade the product based on crosslinked HA which was injected beforehand. Injections of crosslinked HA, because of their gradual disappearance (resorption of the polymer in the tissues over time) have to be repeated at regular intervals, generally from 6 to 12 months, in order to maintain the efficiency of the treatment. Non-crosslinked hyaluronic acid itself has a short residence time in the skin (a half-life of less than a week), it is degraded in vivo by various factors such as radical, enzymatic, thermal and mechanical degradation. It is indeed the crosslinking which allows it to significantly increase its half-life by slowing down the degradation kinetics of hyaluronic acid according to the factors described above, thus allowing efficiency of the aesthetic treatment which may attain about 12 months.
Intensive scientific research is carried out worldwide in order to develop treatments based on hyaluronic acid having reinforced performance over time. The goal is notably to have products capable of being degraded less rapidly in order to retain an optimum aesthetic effect over a period as long as possible, while retaining a very high level of security of the injected products.
Other resorbable filling substances exist on the dermo-aesthetics market. Mention may for example be made of products containing calcium hydroxyapatite. These particles are suspended in an aqueous phase which may contain a polymer like carboxymethylcellulose, a derivative of cellulose. The products of this family are injected into or under the dermis in order to fill the wrinkles or restore the volume of various areas of the body and in particular the face. They show a high level of biocompatibility, which justifies the absence of an allergy test before injection. For these products, very few secondary effects or complications are reported and a duration of efficiency of the order of 12 months or more is observed. From the point of view of resorption, the aqueous phase is rapidly removed from the treated area and the hydroxyapatite particles are degraded and metabolized by macrophages over time.
A stimulation of the endogenous production of collagen by hydroxyapatite particles is also described for these products injected into tissues of the skin.
Unfortunately these products tend to migrate, as described in various scientific publications. This migration poses a problem since it induces premature loss of the aesthetic effect (less biomaterial at the corrected area) and may potentially induce secondary effects (the particles may notably be concentrated in certain portions more or less at a distance from the area to be treated (because of mechanical stresses to which the biomaterial is subject) and locally induce so-called hard areas.
In this context, it is important to make available to practitioners, formulations having remarkable mechanical properties adapted to injections for cosmetic and/or aesthetic purposes having an increased lifetime in the tissues, ready-to-use, and not having the drawbacks described earlier.